The purpose of this study is to elucidate through an adoption paradigm the role of genetic and environmental risk factors in the etiology of drug abuse. Past work on this project has established the roles of genetic factors for antisocial personality and environmental factors as determinants of adult drug abuse/dependency. During this competitive renewal we propose to study the effects of genetic factors for antisocial personality and a variety of environmental factors for their influence on the life course of drug abuse. This will be done by personal interviews of the 743 adoptee subjects (381 male and 362 female) who have been part of the Iowa Adoption Studies. These studies have been ongoing since 1974 so that proposed follow-up subject interviews will be given 10-25 years after the initial interview (all were initially interviewed as adults 18-50 years of age). Retrospective information will be gathered about the subject's lifetime experience with drugs and other substances of abuse. Having a previous interview will allow for determination of reliability of recall for a number of items in the lifetime drug experience, e.g., age at first use or age at first problem. The age spread of subjects will allow for control of secular changes which are important in altering trends in drug use behavior. Focus of the analysis will be upon the behavioral trajectory from biologic background of antisocial personality, through adoptee aggressivity and conduct disorder to adult drug use and comorbid antisocial personality. This is an important pathway leading to substance abuse as evidenced by the large number of antisocials in the country's correctional systems who are incarcerated for drug-related crimes. Study variables have been selected on the basis of their demonstrated importance in drug abuse in our preliminary studies, their potential clinical significance, and their ability to illuminate the personal dynamics which lead to important changes in drug taking behavior, such as cessation of abuse. Information from this proposed study could lead to changes in drug prevention methods as well as indicate long term prognosis for this sizable population. Analysis will involve a number of multivariate techniques including Cox's curve fitting, logistic regression correlating long term behaviors with genetic and environmental factors while controlling for confounds.